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Myoclonus-dystonia syndrome (MDS) is characterized by bilateral, alcohol-sensitive myoclonic jerks, involving predominantly the arms, neck, and axial muscles, and relatively mild dystonia - usually torticollis and/or writer`s cramp - in some patients. Onset of abnormal movements is usually in the first or second decade of life. In addition to motor symptoms, patients often show psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior and alcohol-abuse. The disease is caused by mutations in the gene for epsilon-sarcoglycan (SGCE), which is located on chromosome 7q21. The mechanism, by which SGCE mutations cause MDS is unknown. All mutations identified so far are likely to lead to a loss of protein function. The disease is transmitted as an autosomal-dominant trait. The inheritance pattern of MDS indicates that inactivation of one parental allele may contribute to epsilon-sarcoglycan deficiency. Pedigree analysis in MDS-families showed a marked difference in penetrance depending on the parental origin of the disease allele, with reduced penetrance occurring predominantly if the disease allele is transmitted by the mother. This pattern is suggestive of a maternal imprinting mechanism (i.e. inactivation of the maternally inherited allele, presumably by methylation) which has been demonstrated in the mouse SGCE gene and has now also been shown in humans. |